THE CRYSTAL-STRUCTURE OF STAPHYLOCOCCAL-ENTEROTOXIN TYPE-D REVEALS ZN2-MEDIATED HOMODIMERIZATION()

Bacterial superantigens, including the staphylococcal enterotoxins, ar e the most potent activators of T cells known and have been suggested as a causative factor in Gram-positive shock in humans, Staphylococcal enterotoxin D (SED) is dependent upon Zn2+ for high affinity interact ions with MHC class II molecules and thus SED was to-crystallized with Zn2+, The crystal structure of SED has been determined in two differe nt space groups, at 2.3 and 3.0 Angstrom resolution respectively, The three-dimensional structure of SED is similar to structures of other b acterial superantigens, although this study has revealed that SED has the unique capability of forming dimers in the presence of Zn2+, The h igh affinity Zn2+ site used in dimer formation is located on the surfa ce of the beta-sheet in the C-terminal domain, Tao bound metal ions ar e coordinated by residues from both molecules in the dimer interface a nd thus contribute directly to formation of the dimer, A second Zn2+ s ite is located an the surface close to the domain interface of the mol ecule, The unique feature of SED in forming a Zn2+-dependent homodimer seems to facilitate novel and biologically relevant multimeric intera ctions with MHC class II molecules, as shown by the induction of cytok ine mRNA in human monocytes when exposed to SED and SED mutants.